Bringing Cancer Science to the Bedside

NIH is investing millions of dollars in translational cancer research. How can you get involved?

Edyta Zielinska
Mar 31, 2007
<figcaption>Scientists in the University of Pittsburgh Cancer Institute's molecular and cellular oncology program focus their research on DNA damage and repair and its link to the development and progression of cancer. Credit: COURTESY OF UNIVERSITY OF PITTSBURGH MEDICAL CENTER</figcaption>
Scientists in the University of Pittsburgh Cancer Institute's molecular and cellular oncology program focus their research on DNA damage and repair and its link to the development and progression of cancer. Credit: COURTESY OF UNIVERSITY OF PITTSBURGH MEDICAL CENTER

Craig Jordan began studying cancer stem cells in 1998, when it was still a relatively new field. He soon realized that most drug developers weren't taking advantage of this new science, and he started looking into ways to specifically target leukemic stem cells. His big break came when he discovered that the transcription factor, nuclear factor kappa B (NFkB), was overexpressed in the stem cells because there was already a known agent that inhibitted it: parthenolide. "But that was just the beginning," says Jordan. For the next five years he and his team developed and tested analogs of parthenolide that were soluble and would actively kill stem cells. One...

New opportunities

For Preet Chaudhary, the biggest problem in translational research is the lack of qualified personnel. Chaudhary, who directs the center for translational research at Pittsburgh, says he needs people at all levels who understand what is needed to develop a drug for humans, especially the importance of regulatory requirements. When the principal investigator needs to spend too much time explaining the regulatory concerns, Chaudhary says, it can detract from effective management of the trial.

Translational research in cancer is growing. Just in the past five years, Pittsburgh's cancer institute has hired around 51 researchers to do translational work, "each of which brought anywhere from three to 17 people with them," says Clair Collins, assistant director of the news bureau at Pittsburgh's medical center. In general, institutions need more investigators who are trained in both science and medicine and can grasp translational work and drug development, says David Warner, associate director of the Mayo Clinic's NIH-funded translational program. "It's been recognized in the past several years that we're losing our ability to do good quantities of high-quality clinical research," says Warner.

NIH is making it easier for scientists who are interested in translational research but lack the experience. As a requirement for receiving NIH's Clinical and Translational Science Awards, institutions must create formal training and degree programs for its scientists and clinicians to get up to speed on clinical trials. "Institutions will [soon] be providing this type of clinical research education and an expanded menu of options," from full-fledged PhD degrees to an MS for medical doctors and researchers, as well as certificate programs that offer fast-track courses in drug development, says Warner.

<figcaption> Credit: COURTESY OF UNIVERSITY OF PITTSBURGH MEDICAL CENTER</figcaption>
Credit: COURTESY OF UNIVERSITY OF PITTSBURGH MEDICAL CENTER

Until now scientists and physicians relied on individual career-development NIH grants that allow them to take time off their degrees to learn about clinical research. Jennifer Grandis, an otolaryngologist at the University of Pittsburgh, took a year off towards the end of her residency to do research in a molecular biologist's lab at the cancer center. "After I became competent in doing the surgery, I thought, 'this isn't enough,'" she says. "I wanted to understand how to prevent these tumors." She sees patients one day per week and does surgery one day per week, but the rest of her time is devoted to clinical research. She expects to start a Phase I trial of a new compound later this year.

"[These degrees are] going to be the future," says Paul LaCelle at Rochester University. "A PhD in genetics [alone] won't be all that sought after." The master's program at Rochester is starting small, taking four graduate students per year and two PhD students. They expect the PhD program will be approved this summer.

Chaudhary hopes to retain in his own labs some of the students trained through Pittsburgh's programs. He says he looks forward to working with excellent cancer researchers who are well versed in the intricacies of clinical trial protocols.

Ongoing concerns

Some scientists say they shy away from translational cancer work, fearing they'll get lost in the crowd of investigators needed to bring a drug to the clinic. Researchers typically measure their progress by the number of publications to their name, but clinical trials often take more time to plan and execute than other projects, which limits the number of studies in which scientists can participate. And with many coauthors, individual scientists share a smaller slice of "glory pie" when involved in a set of significant findings. "There has been a lot of resistance by researchers to shift resources from basic [science] to do clinical science," says Francesco Marincola, editor in chief of the Journal of Translational Medicine. Warner expects that to change when translational research is made into a distinct academic discipline through the specialized degree programs.

Some institutions aren't waiting for the reputation of these programs to trickle down. At the Abramson Cancer Center, June says many at his institute are starting to think about how to promote clinical researchers who will have fewer publications to show for their efforts. "It's a national issue," he says. "We're going to have to learn how to promote people like this. [Translational research] is a new specialty."

SO YOU WANT TO DO TRANSLATIONAL RESEARCH? HERE'S HOW TO DO IT RIGHT.

Learn to speak and think like a clinician.
Researchers often fail to ask questions that are realistic to execute in a human trial, whereas clinicians have trouble complying with good scientific practice and often want to modify treatment midtrial, says Francesco Marincola, editor and chief of the Journal of Translational Medicine. Take a course or two to help fill you in on the details of conducting clinical trials.

Anticipate the details.
As the principal investigator of a clinical trial at the University of Pittsburgh, Jennifer Grandis was surprised to find that she was responsible for all the details of the trial. For example, if a nurse forgot to take a patient's blood pressure after the experimental treatment, Grandis was held accountable. She quickly learned to write clinical protocols that would let her monitor all aspects of the trial as it progressed.

Look beyond small biotech.
Robert Bast, vice president of translational research at M.D. Anderson Cancer Center in Houston, says that he's heard of several instances where private companies go out of business, leaving the research team without a drug to carry out the trial. If small biotech makes you nervous, consider going through a government agency to manufacture a drug. The National Cancer Institute offers infrastructure support (but not grant money) for drug production via the Rapid Access to Intervention Development program. Bast predicts that the program might expand to include orphan drugs.

Bring in Big Pharma and clinical scientists early.
Basic researchers benefit from the early input of clinical scientists, who can help guide research on projects most likely headed for clinical success. "Our weekly group meetings were attended by scientists with both basic and clinical research backgrounds," says Tilo Grosser from the University of Pennsylvania. "Questions were asked that got me thinking [about] how the observations I made in my experimental model systems could best be followed-up in humans," he says. "I realized only much later that this experience was kind of a poster-child for translational research training."